Sex Differences in Long-Term Outcomes of Left Atrial Appendage Closure-Analysis from the LEADER Registry

Background: Percutaneous left atrial appendage closure (LAAC) provides an alternative to oral anticoagulation (OAC) in atrial fibrillation (AF) patients who are at high bleeding risk. Prior studies have suggested sex-related differences in procedural outcomes, with women demonstrating higher peri-procedural complication rates. Data on long-term outcomes, however, remain inconsistent. Methods: We analyzed 407 consecutive patients with AF who underwent LAAC between 2010 and 2023 in four Israeli medical centers participating in the LEADER registry. Baseline characteristics, procedural data, and clinical outcomes were compared between men and women. The primary efficacy endpoint was ischemic stroke or systemic embolism at 1 year. The primary safety endpoint was a composite of all-cause mortality, procedural complications, or major bleeding at 1 year. Results: Of 407 patients, 285 (70%) were men and 122 (30%) were women. The mean age was 77 ± 8.4 years with similar CHA₂DS₂-VASc and HAS-BLED scores across sexes. Device implantation exceeded 99% in both sexes. Major peri-procedural complications occurred in 6.4% overall, without significant sex-based differences (men 7.0%, women 4.9%, p = 0.51). At 1-year follow-up, Kaplan-Meier estimates for the primary efficacy endpoint of ischemic stroke/systemic embolism (2.6%), the primary safety endpoint (19.2%), major bleeding (8.9%), and all-cause mortality (9.3%) were comparable between men and women (all p > 0.1). Conclusions: In contrast to prior large registries reporting higher peri-procedural risk in women, this real-world multicenter experience demonstrated no significant sex differences in either peri-procedural or long-term outcomes following LAAC. These findings support LAAC as an effective and safe stroke-prevention strategy in AF, irrespective of sex.